The purpose of this project is to delineate the mechanisms involved in regulating immune response in filarial and nonfilarial disease states. Immunoregulatory studies have examined the phenomenon of antigen-specific anergy in microfilaremic patients by showing this anergy to be a result of a diminished frequency of proliferating cells to parasite antigen and of the production of the antiproliferative cytokines, IL-10 and TGF-beta. Filter immunoplaque assays for the major cytokines have been developed and used to demonstrate that in helminth infections of humans there is an expansion of Th2 CD4+ cells. The phenotypic characterization of these TH2 CD4+ cells has shown them to be CD45RO+ HLA-DR+ CD27-. The underlying genetic basis for the immune responses to certain parasite antigens is currently being studied.